头孢吡肟/阿维巴坦M-H肉汤中浓度测定方法学建立及在体外动态PK/PD模型中的应用OA北大核心CSTPCD
Development and validation of a method for quantitation of ce-fepime/avibactam in M-H broth:application to antibacterial activity using in vitro PK/PD Model
目的:建立头孢吡肟和阿维巴坦在Mueller-Hinton(M-H)肉汤中浓度测定方法,并于头孢吡肟/阿维巴坦体外动态药代动力学/药效学(phar-macokinetic/pharmacodynamic,PK/PD)模型 中进行初步应用.方法:采用高效液相色谱法(HPLC)对M-H肉汤中头孢吡肟进行测定;采用液质联用法(LC-MS/MS)对M-H肉汤中阿维巴坦进行测定.建立头孢吡肟/阿维巴坦2.5gq8h给药方案下体外动态PK/PD感染模型,进行头孢吡肟/阿维巴坦抗碳青霉烯类耐药肺炎克雷伯菌(carbapenem-re-sistant Klebsiella pneumoniae,CRKP)抗菌作用研究.结果:头孢吡肟和阿维巴坦在0.5-120 μg/mL和0.1-25 μg/mL线性关系良好(r=0.999),定量下限浓度为0.5、0.1 μg/mL,肉汤培养基中头孢吡肟和阿维巴坦的的提取回收率分别为88.0％～101.7％和90.9％～95.2％.日内、日间RSD均小于5.2％.在体外PK/PD模型中,头孢吡肟和阿维巴坦具有良好的拟合度,实测浓度在理论浓度的± 20％范围内.对于 MIC=8 μg/mL和 MIC=16 μg/mL的CRKP,头孢吡肟阿维巴坦2.5 gq8 h的给药方案在24 h时菌落分别下降2.783 Log10 CFU/mL、1.325 Log10 CFU/mL.结论:本研究建立的头孢吡肟及阿维巴坦在肉汤中浓度测定方法灵敏度高、稳定性好.体外动态PK/PD模型显示头孢吡肟阿维巴坦常规给药下对MIC≤8 μg/mL的CRKP具有较好的抗菌活性.
AIM:To establish a method for quanti-tation of cefepime and avibactam in M-H broth,and applicated in the in vitro dynamic PK/PD mod-el.METHODS:The cefepime was also determined using the high-performance liquid chromatography method(HPLC),the avibactam was also determined using the liquid chromatography-mass spectrome-try(LC-MS/MS),an in vitro dynamic PK/PD model was established to study the PK/PD relationship of cefepime/avibactam against carbapenem resistant Klebsiella pneumoniae(CRKP).RESULTS:The linear ranges of cefepime and avibactam were good at(0.5-20)and(0.1-25)μg/mL(r=0.999),and the low-er limit concentrations were 0.5 and 0.1 μg/mL.The extraction recoveries of cefepime and avibac-tam in M-H broth were 88.0％-101.7％and 90.9％-95.2％,the relative standard deviation of intra-day precision and inter-day precision were less than 5.2％.The concentration-time curves were well sim-ulated by the PK/PD model.All observed concentra-tions in each experiment were in the range of 20％of the targeted values.For the CRKP of MIC=8 μg/mL and MIC=16 μg/mL,the colony decreased to 2.783Log10 CFU/mL and 1.325Log10 CFU/mLat the cefepime/avibactam 2.5 g q8 h administration after 24 h.CONCLUSION:The determination method of cefepime and avibactam in broth established in this study has high sensitivity and good stability.For the CRKP with MIC≤8 μg/mL,cefepime/avibactam showed that good anti-CRKP activity under routine administration in vitro dynamic PK/PD model.
颜冰倩;郭思维;李尤;田淼梅;徐兵;蒋蓉;李昕
湖南中医药大学,长沙 410208,湖南||长沙市第三医院,长沙 410015,湖南长沙市第三医院,长沙 410015,湖南||长沙市抗菌药物临床应用研究所,长沙 410015,湖南
药学
头孢吡肟阿维巴坦HPLCLC-MS/MS体外动态PK/PD模型
cefepimeavibactamHPLCLC-MS/MSin vitro dynamic PK/PD model
《中国临床药理学与治疗学》 2024 (001)
52-60 / 9
抗耐药微生物药物湖南省重点实验室项目(2023TP1013);湖南省临床医疗技术创新引导项目(2021SK53002)
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